Man and Su contributed equally to this study.
Rapamycin Attenuates Liver Graft Injury in Cirrhotic Recipient—The Significance of Down-Regulation of Rho-ROCK-VEGF Pathway
Article first published online: 20 JAN 2006
American Journal of Transplantation
Volume 6, Issue 4, pages 697–704, April 2006
How to Cite
Man, K., Su, M., Ng, K.T., Lo, C. M., Zhao, Y., Ho, J.W., Sun, C.K., Lee, T.K. and Fan, S.T. (2006), Rapamycin Attenuates Liver Graft Injury in Cirrhotic Recipient—The Significance of Down-Regulation of Rho-ROCK-VEGF Pathway. American Journal of Transplantation, 6: 697–704. doi: 10.1111/j.1600-6143.2005.01231.x
- Issue published online: 20 JAN 2006
- Article first published online: 20 JAN 2006
- Received 3 August 2005, revised and accepted for publication 24 November 2005
- Hepatic stellate cell (HSC);
- liver cirrhosis;
- small-for-size graft
To investigate whether rapamycin could attenuate hepatic I/R injury in a cirrhotic rat liver transplantation model, we applied a rat orthotopic liver transplantation model using 100% or 50% of liver grafts and cirrhotic recipients. Rapamycin was given (0.2 mg/kg, i.v.) at 30 min before graft harvesting in the donor and 24 h before operation, 30 min before total hepatectomy and immediately after reperfusion in the recipient. Rapamycin significantly improved small-for-size graft survival from 8.3% (1/12) to 66.7% (8/12) (p = 0.027). It also increased 7-day survival rates of whole grafts (58.3%[7/12] vs. 83.3%[10/12], p = 0.371). Activation of hepatic stellate cells was mainly found in small-for-size grafts during the first 7 days after liver transplantation. Rapamycin suppressed expression of smooth muscle actin, which is a marker of hepatic stellate cell activation, especially in small-for-size grafts. Intragraft protein expression and mRNA levels of vascular endothelial growth factor (VEGF) were down-regulated by rapamycin at 48 h both in whole and small-for-size grafts. Consistently, mRNA levels and protein expression of Rho and ROCK I were decreased by rapamycin during the 48 h after liver transplantation. In conclusion, rapamycin attenuated graft injury in a cirrhotic rat liver transplantation model by suppression of hepatic stellate cell activation, related to down-regulation of Rho-ROCK-VEGF pathway.